Synthetic hydrogels represent an exciting avenue in the field of regenerative biomaterials given their injectability, orthogonally tunable mechanical properties, and potential for modular inclusion of cellular cues. Separately, recent advances in soluble factor release technology have facilitated control over the soluble milieu in cell microenvironments via tunable microparticles. A composite hydrogel incorporating both of these components can robustly mediate tendon healing following a single injection. Here, a synthetic hydrogel system with encapsulated electrospun fiber segments and a novel microgel‐based soluble factor delivery system achieves precise control over topographical and soluble features of an engineered microenvironment, respectively. It is demonstrated that three‐dimensional migration of tendon progenitor cells can be enhanced via combined mechanical, topographical, and microparticle‐delivered soluble cues in both a tendon progenitor cell spheroid model and an ex vivo murine Achilles tendon model. These results indicate that fiber reinforced hydrogels can drive the recruitment of endogenous progenitor cells relevant to the regeneration of tendon and, likely, a broad range of connective tissues.
The treatment of bone defects with recombinant bone morphogenetic protein‐2 (BMP‐2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low‐dose BMP‐2‐based bone regeneration by mobilizing healing‐associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel‐trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet‐derived growth factor BB (PDGF‐BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF‐BB inhibits BMP‐2‐mediated osteogenesis both in vitro and in vivo. In contrast, smart two‐way dynamic release hydrogels with fast‐release of PDGF‐BB and sustained delivery of BMP‐2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine.
more » « less- NSF-PAR ID:
- 10457729
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Science
- Volume:
- 7
- Issue:
- 7
- ISSN:
- 2198-3844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Basic Protocol 1 : Isolation of bone marrow progenitor cellsBasic Protocol 2 : In vitro differentiation of dendritic cells with GM‐CSFSupport Protocol 1 : Preparation of conditioned medium from GM‐CSF producing J558L cellsBasic Protocol 3 : In vitro differentiation of dendritic cells with Flt3LSupport Protocol 2 : Preparation of Flt3L containing medium from B16‐Flt3L cellsBasic Protocol 4 : Expansion of cDC1s in vivo for use in ex vivo experimentsBasic Protocol 5 : Characterizing resting and activated dendritic cellsBasic Protocol 6 : Dendritic cell stimulation, antigenic cargo, and fixationSupport Protocol 3 : Preparation of model antigen coated microbeadsSupport Protocol 4 : Preparation of apoptotic cellsSupport Protocol 5 : Preparation of recombinant bacteriaBasic Protocol 7 : Immunocytochemistry immunofluorescence (ICC/IF)Support Protocol 6 : Preparation of Alcian blue‐coated coverslipsBasic Protocol 8 : CD8+T cell activation to assess cross‐presentationSupport Protocol 7 : Isolation and labeling of CD8+T cells with CFSE
